The overall objective of this project is to investigate the normal metabolic biochemistry of carnitine during development. The major focus of our work during this year has been identification of hormonal factors which regulate carnitine biosynthesis and uptake of the tissues as the animal matures. We have monitored tissue carnitine concentrations in a large group of rats treated in different ways. Male and female Sprague Dawley rats were obtained at weaning and fed a carnitine-free diet for nine weeks. One group of rats was castrated, a second group of rats was hypophysectomized and a third group was both castrated and hypophysectomized. Another group of normal rats, castrated rats, hypophysectomized rats, and castrated hypophysectomized rats were all treated with dietary carnitine supplementation, daily injections of estradiol, or daily injections of testosterone. Animals were sacrificed and carnitine concentrations determined in the plasma, liver, heart, and skeletal muscle. Our data indicate that tissue carnitine levels are normally regulated at least in part by androgens and estrogens. Tissue carnitine concentrations appear to be under strict hormonal regulation and there may be a different regulatory mechanism for each tissue. Identification of the hormonal factors which determine the plasma, liver, heart and muscle carnitine concentrations would be a significant contribution to our understanding of the clinical cases of carnitine deficiency which are now being reported.